Immunoreactive human skin collagenase has been found to be elevated in tissue extracts of skin of patients with recessive dystrophic epidermolysis bullosa. Furthermore, in two patients with this disease an altered form of collagenase was overproduced in fibroblast culture. If a primary defect in the regulation of synthesis and/or degradation of collagenase were basic to the etiology of recessive dystrophic epidermolysis bullosa, it might be expected that it would be seen in cell cultures from a substantial proportion of these patients. Thus, we plan to examine collagenase expression, measured both as enzyme activity and immunoreactive protein, in fibroblast cultures of patients with recessive dystrophic epidermolysis bullosa. Additionally, similar experiments will be carried out with cells from patients with other, genetically distinct, forms of epidermolysis bullosa to assess the specificity of increased production of the enzyme. Finally, we plan to perform detailed biosynthetic studies both in normal and epidermolysis bullosa cells to determine the nature of the defect leading to increased accumulation of collagenase in cell culture.